The Neuropathology and Genetics Core C of this new National Institute of Neurological Disorders and Stroke (NINDS) Morris K. Udall Parkinson's Disease Research Center of Excellence (Udall Center) at the University of Pennsylvania School of Medicine (PENN) will acquire, preserve and characterize postmortem brain tissue and biological samples collected antemortem from clinically assessed Parkinson's disease (PD) patients as well as controls followed in Core B. PD patients followed in Core B will include those without or with dementia (PDD) and individuals with dementia with Lewy bodies (DLB) as well as the Lewy body (LB) variant of Alzheimer's disease (LBVAD). PD, PDD, DLB and LBVAD represent a spectrum of overlapping neurodegenerative disorders known as ajpha-synucleinopathies that are characterized by prominent central nervous system (CNS) lesions formed by filamentous alpha-synuclein aggregates mainly in neurons or their processes referred to as IBs and Lewy neurites (LNs), respectively. Further, LBVAD, the most common variant of Alzheimer's disease (AD), manifests with neuropathological features of both AD and PDD/DLB. Emphasis here is on implementing proposed postmortem diagnostic criteria.for PDD/DLB using state-of-the-art methods while also assessing the utility of other antemortem diagnostic methodology including both biochemical analysis of biomarkers in biological fluids and molecular genetic strategies. Thus, Core C will work closely with the other Cores and all of the Projects in this Udall Center to play a critical facilitative role in the mission of this Udall Center by evaluating current antemortem diagnoses, improving current diagnostic methods, and providing samples of fresh, unfixed frozen and fixed brain tissues that have been thoroughly characterized to investigators in this and other Udall Centers for research.